Niti Sharma

Study on anti-proliferative effect of benzoxathiole derivatives through inactivation of NF-κB in human cancer cells

To investigate the anti-proliferative effect of a newly discovered NF-kB inhibitor, 6,6-dimethyl-2-(phenylimino)-6,7-dihydrobenzo[d][1,3]oxathiol-4(5H)-one (1a), a series of its analogs (1b-n) were prepared and evaluated for their NF-κB inhibition and anti-proliferative activity against various human cancer cell lines. Slight variation of hydrophobicity by replacement of dimethyl group of 1a at 6-position with bulky isopropyl group and introduction of para-fluoro substitution on 2-phenyl group showed good NF-κB inhibitory activity and anti-proliferative activity. However, excessive increase in hydrophobicity with 2,4,6-trichloro substituents on phenyl group resulted in the loss of both the activities. From the SAR results, 2-phenylimino-6,7-dihydrobenzo[d][1,3]oxathiol-4(5H)-one was identified as the lead scaffold for investigating new anticancer agent through inactivation of NF-κB.

Structure-activity relationship study of arylsulfonylimidazolidinones as anticancer agents.

In an effort to find novel N-arylsulfonylimidazolidinones as highly potent anticancer agent, the structure-activity relationship of ethyl 2-methyl-4-(2-oxo-4-phenylimidazolidin-1-ylsulfonyl)phenylcarbamate was explored through synthesis and evaluation of in vitro cytotoxicity of its analogs against HCT116, A549 and NCL-H460 cancer cell lines. Among the synthesized derivatives, the carbamate analogs (4a-f and 4k-p) exhibited superior cytotoxicity to doxorubicin for all cancer cell lines. The SAR studies of these derivatives confirm that the intact 4-phenyl-l-benzenesulfonylimidazolidinone has a pivotal role as a basic pharmacophore and hydrophobic substitutions only at 2-position of 1-aminobenzenesulfonyl moiety are beneficial for the enhancement of the activity.

A SAR study on a series of synthetic lipophilic chalcones as Inhibitor of transcription factor NF-κB

To define the structural features responsible for the activity of 2,4-dihydroxy-6-isopentyloxychalcone, a newly established inhibitor of LPS induced NF-κB activation (IC(50) = 10 μM), a series of its analogues was prepared and studied for their in vitro activities against LPS induced NF-κB inhibition in RAW 264.7 cells. Among the synthesized derivatives, (E)-1-(2-(decyloxy)-6-hydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (IC(50) = 2.7 μM) and (E)-1-(2-hydroxy-6-(tetradecyloxy)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (IC(50) = 4.2 μM) showed the most potent inhibition. The SAR studies confirmed that the length (C(8)-C(14)) and C-6 position of linear alkyl chain of ring A is an important factor for the inhibitory activity. Hydroxyl group and its location at 4-position on ring B is also important for the inhibition. The α,β-unsaturated ketone moiety appears as a crucial motif of chalcones for the activity.

Ergot Alkaloids: A Review on Therapeutic Applications

Ergot of Rye is a plant disease caused by the fungus Claviceps purpurea which infects the grains of cereals and grasses but it is being used for ages for its medicinal properties. All the naturally obtained ergot alkaloids contain tetracyclic ergoline ring system, which makes them structurally similar with other neurotransmitters such as noradrenaline, dopamine or serotonin. Due to this structure homology these alkaloids can be used for the treatment of neuro related conditions like migraine, Parkinson’s disease etc. For hundreds of years, it has been used in obsctrics and gynecology as an uterotonics. Ergot drugs have important role in treating prolactinomas and type II Diabetes. Their role in cancer treatment has also been established. These drugs constitute an important group of compounds called “Smart drugs” used to improve cognitive function and memory and other age related brain disorders. Structural resemblance with various neurotransmitters allows them to interact with a number of receptors which makes them work on different target thus designing new ergot based drugs with receptor subtype selectivity will be more effective. Review Article Sharma et al.; EJMP, 14(3): 1-17, 2016; Article no.EJMP.25975 2

Exploration of diphenylalkyloxadiazoles as novel cardiac myosin activator

To explore novel cardiac myosin activator, a series of diphenylalkyl substituted 1,3,4-oxadiazoles and 1,2,4-oxadiazoles have been prepared and tested for cardiac myosin ATPase activation in vitro. In all cases, three carbon spacer between the oxadiazole core and one of the phenyl ring was considered crucial. In case of 1,3,4-oxadiazole, zero to two carbon spacer between oxadiazole core and other phenyl ring are favorable. Phenyl ring can be replaced by cyclohexyl moiety. In case of 1,2,4-oxadiazole, zero or one carbon spacer between the oxadiazole and other phenyl ring are favorable. Introduction of hydrogen bonding donor (NH) group at the 2nd position of the 1,3,4-oxadiazole enhances the activity. Substitutions on either of the phenyl rings or change of phenyl ring to other heterocycle are not tolerated for both the oxadiazoles. The prepared oxadiazoles showed selective activation for cardiac muscle over smooth and skeleton muscles.

Safety evaluation of Picrorhiza kurroa rhizome extract by bacterial reverse mutation test

Picrorhiza kurroa is a recognized herb in the Ayurvedic and Chinese system of traditional medicine. It is effective in treating a variety of diseases ranging from digestion problems to paralysis. Thus it is essential to rule out any kind of toxicity, mutagenicity or carcinogenicity in the plant to be used as a medicine. The study was conducted to evaluate ability of Picrorhiza kurroa to induce reverse mutations at the histidine locus in several strains of Salmonella typhimurium in the absence or presence of exogenous metabolic activation system (S9) containing microsomal enzymes. The bacterial reverse mutation assay has been shown to be a sensitive, rapid and accurate indicator of mutagenic activity of a wide range of chemical classes. All bacterial strains showed negative responses over the entire dose range. No significant dose related increase was observed in the number of revertants in the two independent experiments. Based on the results 128 Acharya Balkrishna et al. of this study it is concluded that Picrorhiza kurroa rhizome extract is not mutagenic in the Salmonella typhimurium reverse mutation assay.